Abstract

Background:
The derivation of induced pluripotent stem cells (iPSCs) provides new possibilities for basic research and novel cell-based therapies. Limitations, however, include our current lack of understanding regarding the underlying mechanisms and the inefficiency of reprogramming.

Methodology/principal findings:
Here, we report identification and isolation of a subpopulation of human dermal fibroblasts that express the pluripotency marker stage specific embryonic antigen 3 (SSEA3). Fibroblasts that expressed SSEA3 demonstrated an enhanced iPSC generation efficiency, while no iPSC derivation was obtained from the fibroblasts that did not express SSEA3. Transcriptional analysis revealed NANOG expression was significantly increased in the SSEA3 expressing fibroblasts, suggesting a possible mechanistic explanation for the differential reprogramming.

Conclusions/significance:
To our knowledge, this study is the first to identify a pluripotency marker in a heterogeneous population of human dermal fibroblasts, to isolate a subpopulation of cells that have a significantly increased propensity to reprogram to pluripotency and to identify a possible mechanism to explain this differential reprogramming. This discovery provides a method to significantly increase the efficiency of reprogramming, enhancing the feasibility of the potential applications based on this technology, and a tool for basic research studies to understand the underlying reprogramming mechanisms.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Relative expression of Nanog, Sall4, hTert and Gapdh from three subpopulations of HUF1 cells: SSEA3-negative cells (representing the bottom 10% for SSEA3 expression/detection), SSEA3 intermediate cells (representing the intermediate 80% of cells between the top and bottom 10% for SSEA3 expression/detection) and SSEA3-positive cells (representing the top 10% for SSEA3 expression/detection). Three biological replicates were analyzed for each sample. The relative gene expression value represents the level of gene expression for each sample compared to the overall average for that gene across the three subpopulations.